Study in Cell Implicates Role of Glucose Metabolism in Angiogenesis

		CancerCARE News Archive Featured in the Media JeffNEWS Kimmel Cancer Center

When the drug Avastin was approved by the federal Food and Drug Administration in 2004 as a first-line treatment for metastatic colorectal cancer, it added further proof of the potentially important role of angiogenesis in cancer. Avastin, one of a new era of “targeted therapies,” blocks angiogenesis, the process by which blood vessels form to nourish cell growth in tumors.

Now it is becoming increasingly clear that angiogenesis plays vital roles in the development of a number of diseases, including cancer and diabetes. A team of scientists including Richard G. Pestell, M.D., Ph.D., director of the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia, has shown a clearer path for the role of high glucose levels in angiogenesis, and in turn, diabetic retinopathy.

In a recent issue of Cell, a leading scientific journal, the group, led by Michael Brownlee, M.D., director of the JDRF International Center for Diabetic Complications Research at Albert Einstein College of Medicine in New York, found a molecular connection between high blood sugar inside cells and the beginning of diabetic retinopathy. The team showed that methylglyoxal (MG), a glucose-derived protein that is overproduced in cells damaged by high blood sugar, turns on a gene called angiopoietin-2, which plays a central role in the loss of small blood vessels in the retina.

In diabetic retinopathy, this loss of small blood vessels causes low oxygen delivery to parts of the retina, which then compensates by stimulating new blood vessel growth. This results in intraretinal bleeding and other problems in the diabetic eye that can eventually lead to blindness.

The significant findings suggest that drugs that inhibit MG in cells might help prevent and possibly treat retinopathy. Such drugs might also be useful against cancer because they could cut off the growth of new blood vessels feeding tumors.

“This paper uncovers a new modification to a protein that might represent a new target for therapy that could possibly help patients with diabetes and those with cancer,” says Dr. Pestell, who is also professor and chair of cancer biology at Jefferson Medical College of Thomas Jefferson University.

“We’re very interested in angiogenesis and finding new targets to regulate blood supply,” says Dr. Pestell. “Diabetes and cancer both involve aberrant blood vessel formation. Our labs have been working together on this, and we are particularly focused on finding new therapeutic targets.”

In the late 1990s, angiogenesis-blocking drugs were all the rage. But in subsequent years, the early hype based on dramatic successes in melting tumors in animal studies led to disappointing results in people. More recently, however, newer angiogenesis inhibitors, and different ways of using them, particularly in combination with other drugs, have begun to have some success.

“This new type of protein modification discussed in the paper could play a key role in proliferation and growth connected with angiogenesis, and may lead to the development of new drugs,” says Dr. Pestell.